Antithrombotic and antiplatelet activities of small-molecule alkaloids from Scolopendra subspinipes mutilans

Abstract

The aim of this study was to discover small-molecule anticoagulants from Scolopendra subspinipes mutilans (SSM). A new acylated polyamine (1) and a new sulfated quinoline alkaloid (2) were isolated from SSM. Treatment with the new alkaloids 1, 2, and indole acetic acid 4 prolonged the activated partial thromboplastin time and prothrombin time and inhibited the activity and production of thrombin and activated factor X. Furthermore, compounds 1, 2, and 4 inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these potential in vitro antiplatelet activities, compounds 1, 2, and 4 showed enhanced antithrombotic effects in an in vivo pulmonary embolism and arterial thrombosis model. Compounds 1, 2, and 4 also elicited anticoagulant effects in mice. Collectively, this study may serve as the groundwork for commercializing SSM or compounds 1, 2, and 4 as functional food components for the prevention and treatment of pathogenic conditions and serve as new scaffolds for the development of anticoagulants.

Inhibition of melanogenesis by jineol from Scolopendra subspinipes mutilans via MAP-Kinase mediated MITF downregulation and the proteasomal degradation of tyrosinase

“…Jineol was isolated from specimens using a chromatographic approach16. Briefly, The dried S. subspinipes mutilans (521 g) were extracted with ethanol (5 L × 4) at room temperature and the extract obtained was concentrated under vacuum to yield a brownish ethanol extract (110.0 g).…”

“…This centipede is a recognized medicinal resource for the traditional treatment of spasms, seizure, stroke-related hemiplegia, tetanus, and pain in China and Korea1415. Our chemical investigations on S. subspinipes mutilans revealed the presence of quinoline alkaloids, including 3,8-dihydroxyquinoline (jineol), 2,8-dihydroxy-3,4-dimethoxyquinoline, and scolopendrine16. Jineol (3,8-dihydroxyquinoline) was first isolated from S. subspinipes mutilans in 199617.…”

Biologically active quinoline and quinazoline alkaloids part II

“…All of the compounds showed significant inhibitory effects on platelet aggregation induced by adenosine diphosphate (ADP) at 250 μM. Meanwhile, 8‐hydroxy‐4‐quinolone ( 179 ) (Figure ), from Scolopendra subspinipes multilans , the Chinese red‐headed centipede, exhibited antiplatelet effects . It prolonged activated partial thromboplastin and prothrombin times and inhibited the activity and production of thrombin and activated factor X.…”

Antibacterial Action of Jineol Isolated from Scolopendra subspinipes mutilans against Selected Foodborne Pathogens

“…Jineol was isolated from specimens using a chromatographic approach (Lee et al, 2016). Briefly, the dried ethanol (EtOH) extract (110.0 g) was suspended in water and fractionated successively with ethyl acetate (EtOAc) and then n -butanol (BuOH) to yield EtOAc-soluble (60.0 g) and n -BuOH-soluble (8.0 g) fractions, and residue (40.0 g).…”